title: The p160 ER co-regulators predict outcome in ER negative breast cancer.
abstract: The SRC family of ER co-regulators are frequently overexpressed in breast cancer. Overexpression of AIB1 appears to be linked to hormone resistance in HER2 positive breast cancer. However, the role of these co-regulators in ER negative disease is poorly understood. SRC1, SRC2 and AIB1 expression was determined by immunohistochemical analysis of tissue microarrays constructed from tumours within the Edinburgh Breast Conservation Series (BCS). The BCS represents a fully documented consecutive cohort of 1,812 patients treated by breast conservation surgery in a single institution. Our results demonstrate tumours that overexpress both HER2 and AIB1 were associated with markedly reduced relapse free, distant relapse free and overall survival compared to HER2 and AIB1 only overexpressing tumours irrespective of ER status. In ER negative disease both SRC1 and AIB1 were linked to early relapse and death. The SRC family of ER co-regulators is involved in early relapse and resistance in both ER negative and ER positive breast cancer challenging the conventional concept that this effect is mediated solely via the ER.
authors.affiliation: Breakthrough Breast Cancer, Edinburgh Cancer Research Centre, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UK.
authors.forename: Melanie
authors.initials: M
authors.lastname: Spears
authors.forename: Steffi
authors.initials: S
authors.lastname: Oesterreich
authors.forename: Ilenia
authors.initials: I
authors.lastname: Migliaccio
authors.forename: Carolina
authors.initials: C
authors.lastname: Guiterrez
authors.forename: Susan
authors.initials: S
authors.lastname: Hilsenbeck
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Quintayo
authors.forename: Johanna
authors.initials: J
authors.lastname: Pedraza
authors.forename: Alison F
authors.initials: AF
authors.lastname: Munro
authors.forename: Jeremy St J
authors.initials: JS
authors.lastname: Thomas
authors.forename: Gill R
authors.initials: GR
authors.lastname: Kerr
authors.forename: Wilma J L
authors.initials: WJ
authors.lastname: Jack
authors.forename: Ian H
authors.initials: IH
authors.lastname: Kunkler
authors.forename: David A
authors.initials: DA
authors.lastname: Cameron
authors.forename: Udi
authors.initials: U
authors.lastname: Chetty
authors.forename: John M S
authors.initials: JM
authors.lastname: Bartlett
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D056921:Nuclear Receptor Coactivator 3 / Q000378:metabolism; D056918:Nuclear Receptor Coactivators / Q000378:metabolism*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000032:analysis*; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: D056921:Nuclear Receptor Coactivator 3; D056918:Nuclear Receptor Coactivators; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen